GDP/GTP exchange reaction-stimulating activity of Rabphilin-3A for Rab3A small GTP-binding protein

Rabphilin-3A is a putative target protein for Rab3A, a small GTP-binding protein particularly implicated in neurotransmitter release. Rabphilin-3A interacts more preferentially with GTP-Rab3A than with GDP-Rab3A. Moreover, Rabphilin-3A shows a weak activity to stimulate the GTPase activity of Rab3A and a strong activity to inhibit the Rab3A GTPase-activating protein (GAP)-stimulated GTPase activity of Rab3A. Here, we show that Rabphilin-3A has another activity to stimulate the GDP/GTP exchange reaction of Rab3A. Rabphilin-3A may keep Rab3A continuously in the GTP-bound form by converting again GDP-Rab3A, which may be converted from GTP-Rab3A by Rab3A GAP, to GTP-Rab3A, until the function of Rab3A is accomplished.